Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid (20:5omega3) found primarily in aquatic organisms. We have shown previously that EPA inhibits the growth but is not toxic to human leukemic K-562 cells. In this study, the anti-proliferative effect of EPA on the leukemic cells was further determined and its impacts on cell cycle progression and cyclin expression were investigated. EPA inhibited proliferation of K-562 cells, which was associated with accumulation of G0/G1 cells and down-regulation of cyclin E expression. Cyclin B1-expressing cells were also reduced showing that down-regulation of cyclin expression might be important in the anti-proliferation of EPA.